The treatment of conditions associated with gastric hyperacidity is almost as ancient as recorded history. Peptic and gastroduodenol ulcers have been variously treated both in the past and at present by means of bland diets, the exclusion of certain foods which are mechanically or chemically irritating and foods which do not stimulate gastric secretion.
Additionally, neutralizing drugs, which buffer or neutralize gastric contents; antispasmodics which reduce excessive gastroduodenal motor activity; sedatives which are used to induce general relaxation in ulcer patients; enzyme inhibitors which inhibit pepsin, the proteolytic enzyme secreted by gastric cells; nutritional supplements; mucosal protective agents and histamine antagonists have all been employed. Each of these drugs has its inadequacies as can be seen from the variety of drugs employed.
The most striking feature in the treatment of ulcers, has been a concern with gastric acidity. The rationale of gastric secretory depressant therapy lies in the hope that an agent can be found which will diminish or inhibit the process of hydrochloric acid formation in gastric cells without concomitant damage to these cells or harm to the host. The compounds of the present invention are antisecretory agents having a specific activity against gastric secretion in animals. Thus, they are useful for reducing or inhibiting gastric acid secretion and for the treatment of peptic ulceration. The term peptic ulceration is used in its broad sense, as is conventional in the art, to include both gastric ulceration and duodenal ulceration.
Additionally, these particular compounds are physiologically useful in view of their systemic depressant action upon the central nervous system of vertebrates. Thus, they can be administered either orally or parenterally to mammals for the relief of excessive anxiety and tension. Stress and anxiety are frequently associated as causative or contributing factors to the formation of ulcers. Thus, the compounds described herein are of particular benefit and usefulness not only in reducing gastric secretion, but also in their concomitant effect upon the central nervous system in the reduction of stress and anxiety.
The closest art known to applicant discloses a series of 5-alkyl-4amino-s-triazole-3-thiols stated to have analgetic and antiinflammatory activities, George et al., J. Med. Chem. 14, 335 (1971). Disclosed therein are four compounds containing a triazolothiadiazine nuclear moiety. These compounds lack the cycloalkyl portion of the nucleus and possess completely different pharmacological properties from those compounds claimed herein.